Clinical and genetic risk factors for cystic fibrosis-related liver disease

Objective. The aim of this study was to define the role of possible risk fa ctors for the development of cystic fibrosis (CF)-related liver disease and to analyze the association between liver disease and the different genotyp es present in the Israeli CF patient population. Patients and Methods. All patients followed at the seven CF centers in Isra el were included in this study. Liver disease was determined by persistentl y elevated serum liver enzymes and/or bilirubin, and/or significant ultraso nographic changes suggestive of chronic liver disease. The following clinic al parameters were evaluated: ethnic origin, age at assessment of liver fun ction, sex, history of meconium ileus, pancreatic function, history of dist al intestinal obstruction syndrome, pulmonary function, and cystic fibrosis transmembrane conductance regulator mutation analysis. Results. Of the 288 patients screened, 80 (28%) had liver disease. Of the 2 56 patients with pancreatic insufficiency, 80 (31%) had liver disease compa red with none of the 32 patients with pancreatic sufficiency. Genotype-phen otype correlation was performed on 207 patients carrying identified mutatio ns that were previously classified according to phenotype severity. Liver d isease was found in 56 (32%) of 173 patients carrying mutations associated with a severe phenotype and in 6 (38%) of 16 patients carrying at least one mutation associated with a variable genotype (G85E and/or 5T allele). None of the 18 patients carrying the 3849+10kb C->T mutation had liver disease. Prevalence of liver disease increased with age. No correlation was found b etween liver disease and severity of lung disease, nutritional status, hist ory of meconium ileus, or distal intestinal obstruction syndrome. Conclusion. CF patients who have pancreatic insufficiency and carry mutatio ns associated with a severe or a variable genotype are at increased risk to develop liver disease.